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Alkalinization of Local Anesthetics Increases Speed of Onset Through pH Stabilization at Physiologic Temperature: A Novel Mechanism
Abstract Number: F-20
Abstract Type: Original Research
The addition of sodium bicarbonate (NaHCO3) to local anesthetic (LA) has been shown in vitro and in vivo to increase the speed of onset of neuronal blockade. The increased speed of onset has been attributed to alkalinization of the local anesthetic closer to its pKa, which results in more unionized local anesthetic available to cross into the neuron.1 Temperature also affects the speed of onset, with increased speed of onset at physiologic temperature (PT) vs room temperature (RT).2 However, the potentiation of neuronal blockade by LA with bicarbonate is greater than expected when taking only pH change into consideration.1 We hypothesized that LA at PT would have a pH closer to its pKa, explaining the increased speed of onset, and that addition of NaHCO3 to the warm solution would result in an even larger increase in pH toward pKa.
The pH of 2% lidocaine was compared at RT (20C) and PT (37C) with and without NaHCO3 (10:1 mixture). The LA was placed in a water bath or ice bath set to the appropriate temperature. A Beckman 143800 200 pH meter was used to evaluate the pH of each solution. Each experiment was repeated in triplicate. The pH values were consistent for each temperature across the three measurements to within 0.01. Differences between the pH of the LA solution and the pKa of lidocaine at RT (7.9) and at PT (7.6) were calculated.3
The pH of the LA decreases as the temperature increases to PT (Figure). With increasing temperature, the pH of the LA decreased 0.26 while the alkalinized LA decreased 0.1 At PT the difference between pH and pKa of the LA with and withouth NaHCO3 was 1.49 and 0.65 respectively. The difference at PT was 1.45 and 0.45 respectively.
The small improvement in the difference of pH to pKa in the plain LA (0.04) identifies the mechanism of the clinical difference in onset due to increased temperature. When we compare the LA with NaHCO3 to LA without, we see an exaggerated benefit to the warming. Though the pH of both solutions approach the pKa at PT, the pH of the alkalinized solution is less affected by temperature resulting in a significant improvement in pH toward pKa (0.2). We hypothesize a novel secondary mechanism by which addition of NaHCO3 increases the speed of onset of LA through the stabilization of pH as the LA warms in the physiologic environment.
1.Wong K et al, Anesth Analg 1993 Jan
2.Liu FC et al. Chang Gung Med J 2009 Nov-Dec
3.Sanchez V et al. Anesth Analg 1987 Feb